GRIN2A
Domain
Contains an N-terminal domain, a ligand-binding domain and a transmembrane domain. Agonist binding to the extracellular ligand-binding domains triggers channel gating.
A hydrophobic region that gives rise to the prediction of a transmembrane span does not cross the membrane, but is part of a discontinuously helical region that dips into the membrane and is probably part of the pore and of the selectivity filter.
Function
Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:20890276, PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:28242877, PubMed:36117210, PubMed:38538865, PubMed:8768735). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (By similarity). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:23933818, PubMed:23933819, PubMed:23933820, PubMed:24504326, PubMed:26875626, PubMed:26919761, PubMed:27288002, PubMed:28095420, PubMed:28105280, PubMed:28126851, PubMed:28182669, PubMed:29644724, PubMed:38307912, PubMed:8768735). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:26875626, PubMed:26919761). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (By similarity).
Involvement in disease
Epilepsy, focal, with speech disorder and with or without impaired intellectual development
FESD
An autosomal dominant, highly variable neurologic disorder. Features range from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and intellectual disability to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. The disorder encompasses several clinical entities, including Landau-Kleffner syndrome, epileptic encephalopathy with continuous spike and wave during slow-wave sleep, autosomal dominant rolandic epilepsy, intellectual disability and speech dyspraxia, and benign epilepsy with centrotemporal spikes.
None
The disease is caused by variants affecting the gene represented in this entry.
Rare genetic variations in GRIN2A may be associated with susceptibility to schizophrenia, a severe psychiatric disorder characterized by hallucinations, delusions, disorganized speech and behavior, cognitive impairment, and social withdrawal.
A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2).
GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.
Sequence Similarities
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR2A/GRIN2A subfamily.
Cellular localization
- Cell projection
- Dendritic spine
- Cell membrane
- Multi-pass membrane protein
- Synapse
- Postsynaptic cell membrane
- Multi-pass membrane protein
- Cytoplasmic vesicle membrane
- Expression at the dendrite cell membrane and at synapses is regulated by SORCS2 and the retromer complex.
Alternative names
NMDAR2A, GRIN2A, GluN2A, Glutamate [NMDA] receptor subunit epsilon-1, N-methyl D-aspartate receptor subtype 2A, NR2A, hNR2A